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SPECIAL COMMUNICATIONS: Letters to the Editor-in-Chief

Dietary Nitrate and Muscle Function in Humans

Acute versus Chronic Mechanisms

Coggan, Andrew R.

Author Information
Medicine & Science in Sports & Exercise: April 2018 - Volume 50 - Issue 4 - p 874
doi: 10.1249/MSS.0000000000001489
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Dear Editor-in-Chief,

I read with interest the recent paper of Whitfield et al. (1), in which it was demonstrated that 7 d of dietary nitrate (NO3) supplementation (in the form of beetroot juice [BRJ]) increased peak force and the rate of change in force, and altered the force–frequency relationship, during electrically evoked isometric contractions of the human quadriceps muscle. Unlike comparable previous studies of rodents (2), these effects were observed in the absence of changes in the expression of important Ca2+-handling proteins; that is, the sarcoplasmic reticulum Ca2+-ATPase, calsequestrin, or the dihydropyridine receptor. Although clearly these are not the only proteins that can influence muscle contractile properties, I nonetheless concur with the assessment of Whitfield et al. that posttranslational modifications, not changes in protein expression, likely explain the changes in function that they, as well as others (3,4), have observed in response ≥7 d of NO3 supplementation. I disagree, however, with their conclusion that “future studies should […] include an assessment of changes in function after acute ingestion (i.e., <3 h) of BRJ,” simply because such data already exist. Specifically, we have previously demonstrated that ingestion of 11.2 mmol of NO3 ~2 h before testing increases maximal knee extensor speed and power (as measured using isokinetic dynamometry) by 11% and 6%, respectively, in healthy, young, and middle-age subjects (5). We observed a similar increase in maximal muscle power in athletes (6) and an even greater improvement (i.e., 13%) in patients with heart failure (7), perhaps because such patients are deficient in nitric oxide (NO). Finally, healthy elderly subjects also seem to benefit, at least provided that the dose of NO3 ingested is >125 mmol·kg−1 (8). Thus, that acute dietary NO3 intake can alter human muscle function, well before any significant changes in protein expression could take place, would seem to be well established. Rather, what is lacking, at least in humans, is any firm evidence that chronic supplementation provides any benefits, in terms of muscle contractile properties, above and beyond those simply due to this acute effect. Absent such data, the hunt for the underlying mechanism(s) should logically be focused on NO signaling, for example, via the canonical guanyl cyclase–cyclic GMP–protein kinase G pathway, rather than changes in protein expression.

Andrew R. Coggan

Departments of Kinesiology and Cellular

and Integrative Physiology

Indiana University–Purdue University Indianapolis

Indianapolis, IN

REFERENCES

1. Whitfield J, Gamu D, Heigenhauser GJF, et al. Beetroot juice increases human muscle force without changing Ca2+-handling proteins. Med Sci Sports Exerc. 2017;49(10):2016–24.
2. Hernández A, Schiffer TA, Ivarsson N, et al. Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle. J Physiol. 2012;590:3575–83.
3. Haider G, Folland JP. Nitrate supplementation enhances the contractile properties of human skeletal muscle. Med Sci Sports Exerc. 2014;46(12):2234–43.
4. Justice JN, Johnson LC, DeVan AE, et al. Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: a pilot trial in middle-aged and older adults. Aging (Albany NY). 2015;7:1004–21.
5. Coggan AR, Leibowitz JL, Kadkhodayan A, et al. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide. 2015;48:16–21.
6. Coggan AR, Leibowitz JL, Anderson Spearie C, et al. Acute dietary nitrate intake improves muscle contractile function in patients with heart failure: a double-blind, placebo-controlled, randomized trial. Circ Heart Fail. 2015;8:914–20.
7. Rimer EG, Peterson LR, Coggan AR, Martin JC. Increase in maximal cycling power with acute dietary nitrate supplementation. Int J Sports Physiol Perform. 2016;11:715–20.
8. Coggan AR, Broadstreet SR, Leibowitz JL, et al. Dietary nitrate and muscle power with aging. Med Sci Sports Exerc. 2017;49:S816.
© 2018 American College of Sports Medicine